Evaluating AE Reporting of Two Off-Patent Biologics to Inform Future Biosimilar Naming and Reporting Practices

Drug Saf (2015) 38:687–692 DOI 10.1007/s40264-015-0310-z CURRENT OPINION Evaluating AE Reporting of Two Off-Patent Biologics to Inform Future Biosimilar Naming and Reporting Practices Stella Stergiopoulos1 • Kenneth Getz1 Published online: 25 June 2015  Springer International Publishing Switzerland 2015 Abstract Historical studies of voluntary, spontaneous drug reports show poor attribution of adverse events to generic versions of commonly prescribed medications. As biosimilars enter the market place, it may be similarly difficult to accurately attribute adverse events to their respective reference products. At this time, lack of global consensus with regard to biosimilar naming conventions may result in drug reporting confusion, misattribution of adverse events and insufficient active monitoring of safety signals. Now, with the first biosimilar approval in the USA and many biosimilars expected to be launched globally in the near future, US Food and Drug Administration (FDA) guidance on biosimilar naming conventions will be essential. To inform the FDA and the global drug development community, the Tufts Center for the Study of Drug Development (Tufts CSDD) examined primary suspect reports sent to the FDA’s Adverse Event Reporting System (FAERS) from US reporters for two biologics that have lost patent exclusivity—somatropin and human insulin—and extracted 4703 insulin reports and 6487 somatropin reports from FAERS. The results show that reporting practices are inconsistent between the two biologics that were evaluated and that manufacturer identifiability and traceability are lacking. Ways to improve biosimilar naming conventions and improve reporting practices are suggested. & Kenneth Getz 1 Center for the Study of Drug Development, Tufts University School of Medicine, Boston, MA, USA Key Points Despite strong expected growth in biosimilar approvals over the next decade, there is no global harmonization on biosimilar interchangeability and nomenclature at this time. The US Food and Drug Administration is now considering a number of naming convention options that may facilitate global harmonization. A retrospective study of two off-patent biologics suggests that manufacturer identifiability and traceability are lacking and that better naming conventions are needed to ensure public safety. 1 Biosimilars and Global Interchangeability On 6 March 2015, the US Food and Drug Administration (FDA) approved its first biosimilar drug, Zarxio (filgrastim-sndz) [1]. The pharmaceutical industry widely views this approval as the beginning of a major growth period in biosimilar approvals during the next decade. The FDA noted that Zarxio has been approved as a biosimilar but not as an interchangeable product (i.e. the drug cannot be substituted without healthcare provider approval) [1]. The FDA considers a biosimilar to be interchangeable with the originator biologic (i.e. the reference product) if the drug is a biosimilar, the drug will produce the same clinical result in a patient, and any safety and efficacy risks (e.g. diminished efficacy) of switching to the biosimilar are equal to or less than the risks of staying on the originator product [2]. 688 The European Medicines Agency (EMA) has not made recommendations on biosimilar interchangeability. Instead, it has deferred this decision to the national level [3]. Within European Union member states, France allows for substitution when certain criteria are met (e.g. pharmacists cannot switch patients who have been started on treatment with an originator biologic) [4, 5], and the Netherlands has revised its position to allow substitution provided that the patient has been informed [6]. Elsewhere in the world, Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) is currently debating whether biosimilars could be substituted at the pharmacy level [7]. Both the UK and South Africa prohibit automatic substitution of biosimilars for reference products [8, 9]. Japan also does not allow automatic substitution of biosimilars for originator biologics [10]. Regulatory agencies in the USA and Europe have also noted the importance of tracing adverse events back to the original manufacturer and biologic product for drugs that are allowed to be substituted, for drugs that are not considered interchangeable and for drugs that are considered interchangeable [6, 11, 12]. At this time, policy makers are reviewing biosimilar nomenclature to ensure patient access and safety [13, 14]. 2 Global Biosimilar Naming Conventions Despite much debate and numerous policy suggestions, there is no global harmonization on biosimilar nomenclature at the present time. In 2006, the World Health Organization (WHO) had an informal consultation on the international nonproprietary name (INN) policy for biosimilars [15] and decided ‘‘that the INN policy for biosimilars should be based on scientific considerations and that the INN system should not be altered to reflect regulatory processes. The assignment of INNs should be independent of the regulatory process or of considerations of prescribing interchangeability or the use of INNs in pharmacovigilance’’. In 1991, the WHO also specified different naming conventions for glycosylated and non-glycosylated proteins, whereby a Greek letter is added as a second word to the INN of glycosylated proteins [15, 16]. The WHO also noted that use of the INN system is voluntary [16]. Currently, regulatory agencies have created their own naming conventions for biosimilars. Japan’s policy includes the INN of the reference product, with a biosimilar qualifier and a code for the order of approval [17]. Specifically, biosimilars have a nonproprietary name, which includes the nonproprietary name of the originator biologic, followed by ‘‘(genetic recombination)’’, the INN name and the biosimilar number [18]. The brand name includes the INN, ‘‘BS’’ and then ‘‘Inj Content’’, followed by the company name [18]. S. Stergiopoulos, K. Getz The South African naming convention policy requires that the holder of the certificate of registration (HCR) ‘‘is responsible for ensuring that the product is traceable i.e. reflection of the proprietary name of the product on the adverse event reports’’ [8]. The UK National Institute for Health and Care Excellence (NICE) and the Medicines and Healthcare Products Regulatory Agency (MHRA) recommend ‘‘the use of brand names and lot numbers for traceability … Any guidance on biosimilars will use brand names as substitutability and interchangeability cannot be assumed’’ [9, 19]. The EMA requires that each drug name (the biosimilar name and the originator biologic name) be either the trade name or the name of the active substance (i.e. the INN) together with the company name [20]. For pharmacovigilance, the EMA requires both the trade name and batch number [3, 21–23]. Additionally, the MHRA and EMA both list biosimilars and biological medicines authorized after 1 January 2011 as ‘‘medicines und (...truncated)